Unravelling Microbial Interactions With The Immune System To Help Treat Cancer And Infectious Conditions

The relationship between cancer and infection is complex and reciprocal. Select pathogens can cause (or associate with) cancer, while cancer itself predisposes patients to infections. For instance, ~25% of individuals with chronic lymphocytic leukaemia (CLL) die from sepsis (a severe infection) rather than the malignancy. In my ICBCI Lab, we investigate how microbiota and pathogens modulate immunity and inflammation during steady-state conditions, including asymptomatic infection/carriage, overt infection, and within the tumour microenvironment (TME). Recently, our work has focused on Staphylococcus aureus (SA), an endemic pathogen and frequent cause of sepsis, including in the Trentino region. We hypothesise that SA-derived toxins/components promote CLL tumour activation and progression through the modulation of patient immunity and the TME, thereby increasing susceptibility to sepsis.

Using mouse and human tissue culture models, multiparametric flow cytometry, classical immunological assays, and next-generation sequencing, we examine the phenotype and function of immune (T, B and antigen-presenting) cells and cancer cells from CLL patients, individuals with staphylococcal infections/sepsis, healthy donors, and mice exposed to SA toxins.

This talk will highlight recent evidence showing that SA toxins known a superantigens (SAgs) which notoriously activate T cells, also robustly activate B‑cell tumours in CLL-derived cultures through multimodal modulation of the TME. Further, I will present data from mouse models demonstrating that SAgs favour non-healing pathology of barriers, particularly the skin (a major route of infection in CLL/sepsis), by reshaping immune networks. Finally, I will explore the differential immunological effects of diverse SA SAgs relevant to both asymptomatic carriage and overt infection.

Moving forward, we aim to: (i) untangle distinct mechanisms by which different SA SAgs activate immune and cancer cells; (ii) understand population-level exposure to endemic SA/SAgs and its implications for disease progression; and (iii) design innovative strategies to disrupt SA-driven immunopathology. 

For more details, please refer to:

https://doi.org/10.3389/fimmu.2026.1769061

https://doi.org/10.3389/fimmu.2025.1531059